A differentiation roadmap of murine placentation at single-cell resolution

Abstract

The placenta is one of the most important yet least understood organs. Due to the limitations of conventional research approaches, we are still far from a comprehensive understanding of mouse placentation, especially regarding the differentiation of trophoblast lineages at the early developmental stage. To decipher cell compositions and developmental processes, we systematically profile the single-cell transcriptomes of trophoblast cells from extraembryonic tissues (embryonic day 7.5 (E7.5) and E8.5) and placentae (E9.5–E14.5) at one-day intervals. We identify distinct trophoblast cell types during mouse placentation, including unreported progenitor cells and intermediate precursor cells. An updated differentiation roadmap of mouse trophoblast lineages is presented following systematic transcriptome analyses. Based on transcriptomic regulatory network inference, we specify transcription factors responsible for the regulation of dynamic developmental processes during lineage diversification. We map lineage differentiation trajectories and find that sinusoid trophoblast giant cells arise from the subpopulation of ectoplacental cone cells. We provide a comprehensive single-cell data resource to shed light on future mechanistic studies of the gene regulatory networks governing hemochorial placentation.

The Prl3d1‐Cre mouse line selectively induces the expression of Cre recombinase in parietal trophoblast giant cells

“…High-magnification photographs further showed that tdTomato was expressed in many clustered or scattered giant cells with characteristic large cytoplasms and nuclei (Bevilacqua & Abrahamsohn, 1988) (Figure 2g). P-TGCs are subdivided into primary P-TGCs and secondary P-TGCs (Jiang et al, 2023). In the placenta, the secondary P-TGCs and the spongiotrophoblast layer are together referred to as the JZ (El-Hashash et al, 2010) (Figure 2e).…”

“…To date, TGCs have been divided into four subtypes: spiral artery-associated TGCs (SpA-TGCs), canalassociated TGCs (C-TGCs), parietal TGC (P-TGCs), and sinusoidal TGC (S-TGCs), according to distinct functions and different locations within the placenta (Dunwoodie, 2009). P-TCGs can be further divided into primary P-TCGs differentiated from mural trophectoderm cells and secondary P-TCGs derived from the polar trophectoderm overlying the inner cell mass (ICM) (Jiang et al, 2023). During early gestation, P-TGCs mediate embryo implantation by regulating blastocyst attachment and invasion of the uterine epithelium (Dunwoodie, 2009).…”

Dissecting the Impact of Maternal Androgen Exposure on Offspring Health through Targeting the Androgen Receptor in Developmental Programming

“…[27] To understand the impact of maternal androgen excess on placental development and cell type composition, we deconvoluted our bulk RNA-seq expression data using the cell type specific annotation from single-nuclei data at E10.5. [28] The placentas from PCOS-mice exhibited an increased proportion of decidua stromal cells but decreased proportion of trophoblast cells with a nearly 50% less trophoblast precursor cells compared to the control and flutamide-treatment (Fig. 4c-d, Supplementary Table 5).…”

“…4d-e). The gene expression of Ddr2, encoding the discoidin domain receptor tyrosine kinase 2 and responsible for sensing the extracellular matrix (ECM) collagens, [28] was positively correlated with decidua stroma which was increased in the PCOS-mice placenta (Fig. 4e).…”

Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition

“…The outer region of the ectoplacental cone differentiates to form more TGCs that envelop the whole fetus. 75,76 To comprehensively decipher this complex developmental process in mice, Jiang et al 77 performed single-cell RNA sequencing on trophoblast cells of extraembryonic tissues on embryonic days 7.5 and 8.5, and placental tissues from embryonic days 9.5 to 14.5. In that study, previously unreported progenitor cells and intermediate precursor cells were identified, and the lineage of differentiation trajectory was mapped during placentation in mice.…”